This project includes several studies designed to examine genetic influences and gene-environment interaction with respect to childhood respiratory illness in several different populations throughout the world with different prevalences of asthma. In the spring of 1998, we began collection of buccal cells using intramural funds, as a source of DNA for genetic analysis, among children enrolled in a cohort study of health effects of air pollution in Southern California (USC Childrens Health Study). The collection of buccal cells on the USC Childrens Health Study with intramural funds was so successful that the USC investigators subsequently received extramural RO1 funding to complete the work under the NIEHS/EPA Children Centers. We are now coordinating with the extramural investigators. We are also involved in analysis of data from the childrens health study on family history and physical activity. We are beginning work to initiate a study of genetic susceptibility to childhood asthma among inner city residents of Mexico City. We plan to enroll 200 asthmatic children and their parents in a study of candidate gene associations for asthma in early FY 00 and expand the study to an enrollment of 400. We have also begun a collaboration to collect buccal cell samples on 5000 middle school children in Wuhan , China who are being enrolled in a cohort study to examine smoking and health outcomes including pulmonary function and respiratory symptoms. Nested case-control studies will be done to examine candidate gene association with asthma, chronic respiratory symptoms and impaired growth in pulmonary function. Wuhan China is a low asthma incidence area (estimate of 1-2.5% prevalence). Mexico City is has intermediate rates (about 6%) whereas the Southern California population has the high rates seen in recent US studies (about 12%). Both the Wuhan and Mexico City populations are exposed to high levels of particles other ambient air pollutants as well as antigens such as cockroach, believed to be involved in asthma etiology. The study of populations with high and low incidence of asthma can help identify which proposed risk factors for asthma are etiologically related to the disease. The studies underway will provide a strong basis for comparative studies of gene-environment interaction. - asthma, pulmonary function, suspectibility, polymorphism, air pollution, allergens, antioxidants - Human Subjects